Combination Chemotherapy and Interferon Alfa in Treating Patients With Chronic Myelogenous Leukemia
|ClinicalTrials.gov Identifier: NCT00002598|
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : June 25, 2013
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. Interferon alfa may interfere with the growth of cancer cells.
PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy and interferon alfa in treating patients with chronic myelogenous leukemia.
|Condition or disease||Intervention/treatment||Phase|
|Leukemia||Biological: recombinant interferon alfa Biological: sargramostim Drug: cyclophosphamide Drug: cytarabine Drug: etoposide Drug: methotrexate Drug: mitoxantrone hydrochloride Procedure: bone marrow ablation with stem cell support Radiation: radiation therapy||Phase 2|
- Determine the effectiveness of induction with high-dose mitoxantrone and cytarabine in patients with chronic myelogenous leukemia (CML) in blast crisis.
- Determine the toxicity and activity of consolidation with high-dose cyclophosphamide and etoposide in these patients.
- Determine the toxicity and activity of maintenance with interferon alfa in these patients.
- Determine the efficacy and tolerability of this regimen in these patients.
- Assess minimal residual disease by cytogenetics, DNA gene rearrangement (Southern blotting), and polymerase chain reaction (PCR) in patients treated with this regimen, and use semiquantitative PCR to evaluate the antileukemic activity of subsequent phases of treatment in patients achieving complete remission.
OUTLINE: Patients are stratified by prior therapy for blast crisis (yes vs no).
- Induction: Patients receive high-dose cytarabine IV over 3 hours on days 1-5 and mitoxantrone IV on day 3. Sargramostim (GM-CSF) is administered subcutaneously (SC) (or IV over 4 hours) daily beginning on day 7 and continuing until blood counts recover. After completion of induction, patients with a suitable HLA-identical bone marrow donor undergo allogeneic bone marrow transplantation according to an appropriate IRB-approved protocol. Patients without a donor proceed to consolidation approximately 4 weeks after hospital discharge following induction.
- Consolidation: Patients receive high-dose cyclophosphamide IV on days 1-4 and etoposide IV continuously on days 5-7. GM-CSF is administered SC (or IV over 4 hours) beginning on day 8 and continuing until blood counts recover. Patients achieving a second chronic phase or complete remission proceed to maintenance approximately 4 weeks after hospital discharge following consolidation.
- Maintenance: Patients receive interferon alfa SC on day 1. Treatment with interferon alfa continues daily in the absence of disease progression or unacceptable toxicity.
Patients with CNS involvement at entry or who develop CNS disease during the study receive CNS therapy as outlined below.
- CNS therapy: Patients undergo whole brain irradiation as soon as possible but not concurrently with mitoxantrone. Patients also receive methotrexate intrathecally 3 times a week until the CSF is clear, weekly for 4 weeks, and then monthly for 6 months.
PROJECTED ACCRUAL: A total of 14-30 patients will be accrued for this study within 4 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Masking:||None (Open Label)|
|Official Title:||A PHASE II STUDY OF MITOXANTRONE AND HIGH-DOSE ARA-C FOLLOWED BY INTENSIVE CONSOLIDATION WITH CYCLOPHOSPHAMIDE AND ETOPOSIDE FOR MYELOID BLAST CRISIS OF CHRONIC MYELOGENOUS LEUKEMIA (CML)|
|Study Start Date :||June 1994|
|Actual Primary Completion Date :||June 2004|
|Actual Study Completion Date :||June 2004|
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00002598
|United States, New York|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10021|
|Study Chair:||Mark Adam Weiss, MD||Memorial Sloan Kettering Cancer Center|